Research Affiliates

Mary Hynes, Ph.D.

Dr. Hynes investigates the development of the key cells targeted by Parkinson’s disease: dopaminergic neurons.

Dr. Hynes and colleagues were the first to show that dopaminergic neurons are induced by a molecule called Sonic hedgehog. Her work led to a widely used method involving a combination of this and other molecules to derive dopaminergic neurons from embryonic stem cells. Her research at Rockefeller focuses on identifying molecular markers that distinguish the two types of dopaminergic nerve cells: substantia nigra neurons, which are involved in motor control and die in Parkinson’s disease, and ventral tegmental area neurons, which are part of a reward pathway and are not as affected by the disease. She is studying how to produce substantia nigra neurons from embryonic stem cells and, in better understanding their development, inform possible treatments for Parkinson’s, including neuron transplantation.

Substantia nigra and ventral tegmental neurons are closely related and very difficult to parse, especially in early stages of development. Her recent work has found that certain axon guidance cues, molecules that direct the growth of neurons, are expressed in interesting patterns around the developing dopaminergic neurons. Using a combination of axon guidance receptor expression, guidance cue responsiveness and tract tracing, combined with laser capture microdissection and microchip array analysis, she hopes to identify markers that distinguish the two key populations of dopaminergic neurons.

The work could lead to methods for specifically inducing and dissecting the development of substantia nigra neurons, and a better understanding of guidance cue responsiveness could be used to improve the targeting of transplanted neurons meant to replace those killed off by Parkinson’s disease.